The aim of the project outlined here is to explore the kinin forming system in normal and malignant tissues. Our efforts will be directed toward the isolation and characterization of the tissue activators or prekallikrein and tissue kallikreins. Tissue contain kinin-forming enzymes which are different from the enzymes found in plasma. It is not clear how these enzymes become activated and so far no tissue activators or tissue prekallikreins have been characterized. Our preliminary experiments with various tissues including malignant carcinoid tumors have suggested the existence of activators of prekallikrein and/or tissue prekallikreins. We plan to purify and characterize tissue activators and study their mode of action. The purified enzymes will be used to produce antibodies. The chemical and immunologic characterization of the components of the kinin-forming system in normal and tumor tissue will be carried out.